Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

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dc.contributor.authorTorres, Juan Manuel
dc.contributor.authorMartínez Barricarte, Rubén
dc.contributor.authorGarcía Gómez, Sonia
dc.contributor.authorMazariegos, Marina S
dc.contributor.authorItan, Yuval
dc.contributor.authorBoisson, Bertrand
dc.contributor.authorÁlvarez Carbajal, Rita Lucía
dc.contributor.authorJiménez Reinoso, Anaïs
dc.contributor.authordel Pino, Lucía
dc.contributor.authorRodríguez Pena, Rebeca
dc.contributor.authorFerreira Martín, Antonio
dc.contributor.authorHernández Jiménez, Enrique
dc.contributor.authorToledano, Víctor
dc.contributor.authorCubillos Zapata, Carolina
dc.contributor.authorDíaz Almirón, Mariana
dc.contributor.authorLópez Collazo, Eduardo
dc.contributor.authorUnzueta Roch, José L
dc.contributor.authorSánchez Ramón, Silvia María
dc.contributor.authorRegueiro González-Barros, José Ramón
dc.contributor.authorLópez Granados, Eduardo
dc.contributor.authorCasanova, Jean-Laurent
dc.contributor.authorPérez de Diego, Rebeca
dc.date.accessioned2023-06-19T13:46:06Z
dc.date.available2023-06-19T13:46:06Z
dc.date.issued2014-11
dc.description.abstractHeterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain–containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient’s myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB–mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects.
dc.description.departmentDepto. de Inmunología, Oftalmología y ORL
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economia y Competitividad (MINECO)
dc.description.sponsorshipFundación Lair
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/69220
dc.identifier.doi10.1172/JCI77493
dc.identifier.issn0021-9738 (print), 1558-8238 (online)
dc.identifier.officialurlhttps://doi.org/10.1172/JCI77493
dc.identifier.urihttps://hdl.handle.net/20.500.14352/34396
dc.issue.number12
dc.journal.titleThe Journal of Clinical Investigation
dc.language.isoeng
dc.page.final5248
dc.page.initial5239
dc.publisherAmerican Society for Clinical Investigation
dc.relation.projectIDSAF2011-24235
dc.rights.accessRightsrestricted access
dc.subject.ucmInmunología
dc.subject.unesco2412 Inmunología
dc.titleInherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity
dc.typejournal article
dc.volume.number124
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery247c0f89-3149-4752-a21d-49057c0a41b0
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